Abstract: The overall objective of the COBRE Phase-2 for Dietary Supplements and Inflammation (CDSI) at the University of South Carolina (USC) is to continue to build on the success of Phase-1 and advance the research infrastructure specifically in the area of dietary supplements and inflammation by promoting multi-disciplinary research pursued by junior investigators so that they become highly competitive in obtaining NIH R01 grants and similar type of extramural funding to pursue their research. The overall objective is to investigate how botanicals can attenuate inflammation and be used to prevent and/or treat inflammatory diseases. The CDSI will test the overarching hypothesis that botanicals or their constituents regulate inflammation through epigenetic regulation of immune cell functions. In Phase-1, we have made outstanding progress in the successful transition of all of our junior faculty into extramurally-funded investigators. Additionally, we were successful in securing NIH Complementary and Alternative Medicine (CAM) Center (P01) for Epigenetic Regulation of Inflammation, in which ?graduated? faculty are leading the projects, thereby paving the path towards sustainability of CDSI. Thus, the CDSI will complement the CAM Research and create a unique niche at USC in inflammation research. The main goal of COBRE Phase-2 is to establish multi-disciplinary research that will identify the epigenetic mechanisms through which botanicals modulate inflammation so that they or their analogs can be used to prevent and/or treat inflammatory diseases. The US population spends ~$33.9 billion/year on CAM, of which ~$20 billion is on dietary supplements. It is becoming increasingly clear that inflammation plays a critical role in the pathogenesis of not only autoimmune diseases but also a wide range of clinical disorders including cardiovascular diseases, neurodegenerative disorders, obesity, aging and cancer. Thus, understanding the mode of action of botanicals or their constituents on inflammation, could lead to novel treatment modalities with far ranging clinical implications. The CDSI goal will be accomplished through promotion of multi-disciplinary research pursued by 4 junior faculty in the area of inflammatory diseases, through highly structured mentoring of each by a senior faculty and a recently graduated faculty member of the COBRE Phase-1. The junior faculty will have access to state-of-the-art research core facilities that include Flow Cytometry, Microscopy and Imaging Core, and Bioanalytical Core, to aid epigenetic studies. The program will be evaluated by an External Advisory Committees consisting of nationally recognized scientists. Additionally, through institutional support, 5 new tenure-track junior faculty will be recruited and mentored at USC to bolster and advance inflammation research. The long term objective of the CDSI would be to build a self-sustaining, nationally and internationally recognized multi-disciplinary Center for dietary supplements and inflammation research, by promoting innovation, faculty entrepreneurship, collaborative research projects such as PPGs and Institutional training grants, and clinical/translational research.